We have compared zebrafish genome organization with that of humans and found that large chromosome segments have been conserved for the 430 million years since the divergence of human and zebrafish lineages (Postlethwait et al., 1998). At least four copies of some paralogous chromosome segments exist in zebrafish, and they generally correspond to orthologous chromosome segments in mammals, suggesting that two large scale gene duplication episodes, perhaps whole genome duplication events, occurred prior to the divergence of fish and mammal lineages. We are now investigating regulation of duplicate hox genes.

Our cloning and mapping of the zebrafish hox clusters (Amores et al., 1998) showed that zebrafish has two copies of many human chromosome segments, suggesting an additional genome duplication event in the zebrafish lineage. Comparisons with the hox clusters of pufferfish (Amores et al., 1998; Aparicio et al, 1997 suggested that this even occurred before the divergence of pufferfish and zebrafish lineages at the base of the teleost radiation. A speculative hypothesis is that the extra genes spawned by this duplication facilitated the divergence of teleosts into the most species rich group of vertebrates.

Current work focuses on developmental genomics of zebrafish, the pufferfish Spheroides nephalus, and the larvacean urochordate Oikopleura dioica. For example, we have recently cloned from Oikopleura a homologue of the brachyury gene (Bassham and Postlethwait, 2000). In mouse and zebrafish, brachyury is required for the development of the notochord, the eponymous feature of the entire phylum. The developmental analysis suggests ancestral functions for this gene.

Future work will focus on the developmental roles of genes in Oikopleura and their duplicated orthologues in vertebrates, especially those genes necessary for the development of large brains, neural crest, and placodes, to understand the relationships of gene duplication and the evolution of novel morphologies.

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